Digitalis capsule



Patented Oct. 6, 1 942 W Quincy, Mass assignors to UnitedDrug Company, Boston, Mass., acorporation ofDelaware e 7 No Drawing. Application January 27,1941, I V SerlalNo. 376,124.,

5 Claims. (cum-e5)" This invention relates to digitaliscapsules, and more particularly to such capsules formed from gelatin and enclosing a specific? dosage of digitalis drug. V

provision of capsules of the indicated type'which remain stable over extended periods of time: the provision of such capsules which may be stored under normal conditions for I extended periods of time-and still retain their initial potency; the 1 invention-may be kept on drug store shelves, or provision of capsules of the indicated type which under otherwise normal storage conditions until may be administered in the usualmanner, and required. A fphysician who prescribes a given which are eflective without substantial loss of dosage ofdigitalis may be certain that the com 7 time; the provision of such capsules which are position of the present invention will provide effective on'the human organism as quickly as such a dosage, although it has been stored over the present commercial forms of digitalis; and an extended period. V

the provision of capsules of the classindicated Digitalis is, inaccordance with the present inwhich are easy and inexpensively prepared from vention, prepared in the form of plasticized gelawidely available materials. Other objects will tin capsules. These capsulesare of the cusbe in part obvious and in part pointed out here-.- tomary type, namely, a plasticized gelatin outerinafter. layer enclosing a given dosage of the medicinal The invention accordingly comprises the' eleingredient. The digitalisitself is suspended in ments and combinations of elements, steps and .a'blandjnert vehicle which is liquid over at least sequence of steps, features of construction and part of the temperaturerange between 40 and manipulation, and arrangements of p'artsjwhich 25.65 .C. The vehicle" must notbe hy'drophilic, and" will be exemplified in the structures and methods it must be, of, suitable specific gravity to retain hereinafter described, and the scope of the applithe digitalis particles suspended during capcation of which will be indicated in the following sulati'on. This vehicle is preferably digestible. claims. V It has beeni found that mineral oil, cotton seed Digitalis is a valuable medicinal widely vemoil, mixtures of edible vegetable oils, either hy ployed in the treatment of certain forms of heart drogenated or unhydrogenated, or similar edible afllictions. "As is true of many drugs, digitalis is fatty acid glycerides areyquite "suitable as :sus toxic in dosages substantially above the .therpending agents for .use; inthe present invention. apeutic dose. It is therefore important that the The preferred vehicle 'is a. mixture of hydro-P- potency of a 'given'quantity ofdrugbe established genated andlunhydrogenated'fatty acid glycerand known to the physician administering it. l ides; '3 r v -Digitalis fis customarily marketed, either in The digitalisleaf,-. preferably -finely divided-fi the form of a tincture, or in the form of tablets such as to 80-100 mesh, and dried-toa moisture formedfrom the powder of dried digitalisleaves. content of not more than"l0%' and preferably of The tincture so formed is, however, subject to 40 not more than 4 to 5%, is suspended in a suitdeterioration with the passage of time. The able proportion of a vehicle of the class indicated. same is true of the tablets unless thoroughly dry The proportion of vehicle and digitalis may be and stored in air-tight containers. As a result, varied over relatively wide ranges, but the vethese tablets or the tincture cannotbestored under hicle must be present in suflicient proportion to normal conditions for any extensive period. The surround the digitalis particles. The viscosity tincture is customarily made up fresh at he of the mixture should be such that the drug does quent intervals, in order to insure administration not sediment during capsulation. The particles of the proper dosage. Moreover, as the United of digitalis are uniformly dispersed in the vestates Pharmacopoeia states, the digitalis leaves hi l p f r bly a mixture of Ve e able il an themselves must be preserved thoroughly dried, hydrogenated oil, and" the product may be diin air tight containers" to minimize loss of ef-. luted with additional quantities of oil to form fectiveness. Such expedients, although ex-' the desired dosage. Thus a given capsule size pensive, are essential to maintain the potency of may contain one-half grain, one grain, one andthe tincture or tablets subsequently formed from one-half 'grainsetc.,' of active units, dependent i the digitalis leaves. The tincture and tableted Among the objectsof this invention are the powder, must not only be:made up fresh a short time before useand/orrigidly protected after preparation, but the principal ingredient, the digitalis leaves, must likewise be rigidly protected. 'According to the present invention a digitalis preparationyis providedwhich" may be stored over extended periods of time, ,and which will show substantially no deterioration after an I extended storage. 7 The preparation of the present upon particular. manufacturingi convenience..

cated, fluid at these and closing a leted digitalis particles show marked deterioration under these conditions, unless rigidly protected both from moisture and air. In fact, it has been found that even temporarily opening given container of powdered digitalis a limited number oftimes, such as is necessar'y in. withdrawinga portion of the drug for Zthe preparation of a tinctureor infusion thereof,-

is suflicient to cause marked deterioration in the remainder. This deterioration occurs even though an air-tight and moisture-proof container-is employed, and eventhough the drug has formed as described, is then formed into a gelatin capsule in the customary manner. The usual temperatures for capsulation maybe employed, which in general are from 40-65" C. The digitalis suspension in the inert vehicle is 'a'sindiis easily made into gelatin capsules.

Gelatin capsules formed in accordance with the present invention'and having digitalis suspended in an inert-bland water-free vehicle of the type indicated have been tested, both promptlyafter manufacture and after storage .under normal drug store storage conditions for an extended periodoftime. I

It has been found that capsules prepared in accordance with the instant invention present the drug in a ready assimilable form. It has been foundthat the digitalis is efiective'a's'quickly afteradmiriistration as is the case when the customary tincture or tableted digitalis are administered.

In order to test the time required for the digitalis to become effective, precisely-equal amounts of the drug prepared from the same lot of digithree dosage forms;

talis powder were made into namely, gelatin capsules in accordance with the present invention, a tincture, and digitalis tablets in which the material wasmerely tableted. The

latter two were made inaccordance with standard pharmacal practice. were given orally to guinea pigs and cats, in sufficient quantity to be toxic. The length of time required for death was in each instance similar. As the time required for the toxic eil'ect to become lethal shows that the rate of absorption was'the same, the digitalis preparation of the present invention is effective as promptly as thecustomary formsfor presenting digitalis. V

Digitalis capsuleswhich had beenstored over a period as long as a year; were tested for'potency, and ,for absorption rate. It was found in each instance that no appreciable decrease; either-in;

potency or absorption rate,had occurred, although these'capsules were stored under-customary dru'g temperatures, and therefore 1 invention.

been previously thoroughly dried, as required by thePharmacopoeia. No such precautions are re- .quired with the gelatin capsules of the present Theyrmay be stored in open containers in contact with air, yet suffer no appreciable deterioration.

In view of the above, it will be seen that the several objects of the invention are achieved and other advantageousresults attained.

As many changescould be made in the above methods and products without departing from the scope of the invention, :it is intendedthat all V moisture;

. vehicle, slaid'd igitalis Equal dosages of each store storage conditions." The tincture or tabmatter contained in the above description shall be interpreted as illustrative and not in a limiting sense.

'What is claimed is:

1. A'digitalis capsule comprising an outer layer of gelatin enclosing digitalis leaf suspended in an inert, water-free viscous oil -vehi cle,sai d digitalis leaf containing notsubsta'ntially inexcess of 10% 2'. A stable digitalis capsule comprising a gelatin outer layer enclosing digitalis leaf suspended in'an' inertLwatef-free, viscous, digestible oil leaf containing not substantially' in excess'of:l0% moisture.

3. A gelatin capsule comprising an outer layer of gelatin and a central portion comprising digitalis leaf suspended in an inert, water-free, vehicle' which is fluid at a capsulating temperahim, said digitalis leaf containing not substantiallyin excess of 10% moisture.

4. A gelatin capsule comprising an outer layer 1 of gelatin and a central portion comprising digitalis leaf suspendedin a mixture of hydrogenated and unhydrogenated vegetable oils, said digitalis leaf containing not substantially in excess of 10%moisture. I n

5.'A gelatin capsule comprisingan outerlayer of gelatin and a central portion comprising powder'ed'digitalis leaf suspended in an inert, ,waterfree, oil vehicle which'isfluidat a capsulating temperature, sai d gitalis leaf substantially in excess'of 10% moisture.

JOSEPHA. HAIL-ER.

CLARE O. EWING.

containing not 1 

